INAPSINE (Page 2 of 3)

Impaired Hepatic or Renal Function

INAPSINE should be administered with caution to patients with liver and kidney dysfunction because of the importance of these organs in the metabolism and excretion of drugs.

Pheochromocytoma

In patients with diagnosed/suspected pheochromocytonia, severe hypertension and tachycardia have been observed after the administration of INAPSINE (droperidol).

Drug Interactions

Potentially Arrhythmogenic Agents

Any drug known to have the potential to prolong the QT interval should not be used together with INAPSINE. Possible pharmacodynamic interactions can occur between INAPSINE and potentially arrhythmogenic agents such as class I or III antiarrhythmics, antihistamines that prolong the QT interval, antimalarials, calcium channel blockers, neuroleptics that prolong the QT interval, and antidepressants.

Caution should be used when patients are taking concomitant drugs known to induce hypokalemia or hypomagnesemia as they may precipitate QT prolongation and interact with INAPSINE. These would include diuretics, laxatives and supraphysiological use of steroid hormones with mineralocorticoid potential.

CNS Depressant Drugs

Other CNS depressant drugs (e.g., barbiturates, tranquilizers, opioids and general anesthetics) have additive or potentiating effects with INAPSINE. Following the administration of INAPSINE, the dose of other CNS depressant drugs should be reduced.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity studies have been carried out with INAPSINE. The micronucleus test in female rats revealed no mutagenic effects in single oral doses as high as 160 mg/kg. An oral study in rats (Segment I) revealed no impairment of fertility in either male or females at 0.63, 2.5 and 10 mg/kg doses (approximately 2.9 and 36 times maximum recommended human iv/im dosage).

Pregnancy

Category C

INAPSINE administered intravenously has been shown to cause a slight increase in mortality of the newborn rat at 4.4 times the upper human dose. At 44 times the upper human dose, mortality rate was comparable to that for control animals. Following intramuscular administration, increased mortality of the offspring at 1.8 times the upper human dose is attributed to CNS depression in the dams who neglected to remove placentae from their offspring. INAPSINE has not been shown to be teratogenic in animals. There are no adequate and well-controlled studies in pregnant women. INAPSINE should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

There are insufficient data to support the use of INAPSINE in labor and delivery. Therefore, such use is not recommended.

Nursing Mothers

It is not known whether INAPSINE is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when INAPSINE is administered to a nursing mother.

Pediatric Use

The safety of INAPSINE in children younger than two years of age has not been established.

ADVERSE REACTIONS

QT interval prolongation, torsade de pointes, cardiac arrest, and ventricular tachycardia have been reported in patients treated with INAPSINE. Some of these cases were associated with death. Some cases occurred in patients with no known risk factors, and some were associated with droperidol doses at or below recommended doses.

Physicians should be alert to palpitations, syncope, or other symptoms suggestive of episodes of irregular cardiac rhythm in patients taking INAPSINE and promptly evaluate such cases (see WARNINGS, Effects on Cardiac Conduction).

The most common somatic adverse reactions reported to occur with INAPSINE (droperidol) are mild to moderate hypotension and tachycardia, but these effects usually subside without treatment. If hypotension occurs and is severe or persists, the possibility of hypovolemia should be considered and managed with appropriate parenteral fluid therapy.

The most common behavioral adverse effects of INAPSINE (droperidol) include dysphoria, postoperative drowsiness, restlessness, hyperactivity and anxiety, which can either be the result of an inadequate dosage (lack of adequate treatment effect) or of an adverse drug reaction (part of the symptom complex of akathisia).

Care should be taken to search for extrapyramidal signs and symptoms (dystonia, akathisia, oculogyric crisis) to differentiate these different clinical conditions. When extrapyramidal symptoms are the cause, they can usually be controlled with anticholinergic agents.

Postoperative hallucinatory episodes (sometimes associated with transient periods of mental depression) have also been reported.

Other less common reported adverse reactions include anaphylaxis, dizziness, chills and/or shivering, laryngospasm, and bronchospasm.

Elevated blood pressure, with or without pre-existing hypertension, has been reported following administration of INAPSINE combined with SUBLIMAZE (fentanyl citrate) or other parenteral analgesics. This might be due to unexplained alterations in sympathetic activity following large doses: however, it is also frequently attributed to anesthetic or surgical stimulation during light anesthesia.

OVERDOSAGE

Manifestations

The manifestations of INAPSINE (droperidol) overdosage are an extension of its pharmacologic actions and may include QT prolongation and serious arrhythmias (e.g., torsade de pointes) (see BOX WARNING, WARNINGS, and PRECAUTIONS).

Treatment

In the presence of hypoventilation or apnea, oxygen should be administered and respiration should be assisted or controlled as indicated. A patent airway must be maintained; an oropharyngeal airway or endotracheal tube might be indicated. The patient should be carefully observed for 24 hours; body warmth and adequate fluid intake should be maintained. If hypotension occurs and is severe or persists, the possibility of hypovolemia should be considered and managed with appropriate parenteral fluid therapy (see PRECAUTIONS).

If significant extrapyramidal reactions occur in the context of an overdose, an anticholinergic should be administered.

The intravenous Median Lethal Dose of INAPSINE is 20 to 43 mg/kg in mice; 30 mg/kg in rats; 25 mg/kg in dogs and 11 to 13 mg/kg in rabbits. The intramuscular Median Lethal Dose of INAPSINE is 195 mg/kg in mice; 104 to 110 mg/kg in rats; 97 mg/kg in rabbits and 200 mg/kg in guinea pigs.

DOSAGE AND ADMINISTRATION

Dosage should be individualized. Some of the factors to be considered in determining the dose are age, body weight, physical status, underlying pathological condition, use of other drugs, type of anesthesia to be used and the surgical procedure involved.

Vital signs and ECG should be monitored routinely.

Adult dosage

The maximum recommended initial dose of INAPSINE is 2.5 mg IM or slow IV. Additional 1.25 mg doses of INAPSINE may be administered to achieve the desired effect. However, additional doses should be administered with caution, and only if the potential benefit outweighs the potential risk.

Children’s dosage

For children two to 12 years of age, the maximum recommended initial dose is 0.1 mg/kg, taking into account the patient’s age and other clinical factors. However, additional doses should be administered with caution, and only if the potential benefit outweighs the potential risk.

See WARNINGS and PRECAUTIONS for use of INAPSINE with other CNS depressants and in patients with altered response.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If such abnormalities are observed, the drug should not be administered.

HOW SUPPLIED

INAPSINE® (droperidol) Injection is available as:

NDC 11098-010-01, 2.5 mg/mL, 1 mL ampules in packages of 10

NDC 11098-010-02, 2.5 mg/mL, 2 mL ampules in packages of 10

NDC 11098-531-01, 2.5 mg/mL, 1 mL vials in packages of 25

NDC 11098-531-02, 2.5 mg/mL, 2 mL vials in packages of 25

STORAGE

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature]. Protect from light.

REFERENCES

  1. Saarnivarra L, Klemola UM, Lindgren L, et al. QT interval of the ECG, heart rate and arterial pressure using propofal, methohexital or midazolam for induction of anesthesia. Acta Anaesthesiol Scand 1990; 34: 276-81.
  2. Schmeling WT, Warltier DC, McDonald DJ, et al. Prolongation of the QT interval by enflurane, isoflurane and halothane in humans. Anesth Analg 1991; 72: 137-44.
  3. Spath G. Torsade des pointe oder die andere Ursache des plotz-lichen Herztodes. Wien: Ueberreuter, 1998.
  4. Riley DC, Schmeling WT, Al-Wathiqui MH, et al. Prolongation of the QT-interval by volatile anesthetics in chronically instrumented dogs. Anesth Analg 1988; 67: 741-9.
  5. McConachie I, Keaventy JP, Healy TF, et al. Effects of anaesthesia on the QT-interval. Br J Anaesth 1989; 63: 558-60.
  6. Lawrence KR, Nasraway SA. Conduction disturbances associated with administration of butyrophenone antipsychotic in the critically ill: a review of the literature. Pharmacother 1997; 17(3): 531-7.
  7. Lischke V, Behne M, Doelken P, et al. Droperidol causes a dose-dependent prolongation of the QT interval. Anesth Analg 1994; 79: 983-6.

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